Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease. Issue 3 (16th March 2023)

• Record Type: Journal Article
• Authors: Schneider, Sven; Poglitsch, Katharina; Morgenstern, Christina; Quint, Tamara; Gangl, Katharina; Sinz, Christoph; Bartosik, Tina; Campion, Nicholas James; Liu, David Tianxiang; Landegger, Lukas David; Tu, Aldine; Stanek, Victoria; Rocha-Hasler, Marianne; Bangert, Christine; Eckl-Dorna, Julia
• Is Part Of: European respiratory journal. Volume 61:Issue 3(2023)
• Publication Date: 2023-03-16
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.01335-2022
• Languages: English
• ISSNs: 0903-1936

Abstract

Background: Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps, asthma and intolerance to NSAIDs. Dupilumab treatment, targeting the interleukin-4 (IL-4) receptor α, significantly reduces polyp burden as well as asthma symptoms. Here we aimed to investigate the effect of dupilumab on aspirin intolerance, burden of disease and nasal cytokine profiles in patients with N-ERD. Methods: In this open-label trial, adult patients with confirmed N-ERD were treated with dupilumab for 6 months. Clinical parameters ( e.g. total polyp scores, quality of life questionnaires, smell test, spirometry), oral aspirin provocation testing and blood, nasal and urine sampling were monitored at regular intervals for up to 6 months after starting dupilumab therapy. Results: Of the 31 patients included in the study, 30 completed both aspirin provocation tests. After 6 months of treatment with dupilumab, 23% of patients (n=7 of 30) developed complete aspirin tolerance and an additional 33% of patients (n=10 of 30) tolerated higher doses. Polyp burden was significantly reduced (total polyp score: −2.68±1.84, p<0.001), while pulmonary symptoms (asthma control test: +2.34±3.67, p<0.001) and olfactory performance improved (University of Pennsylvania Smell Identification Test: +11.16±9.54, p<0.001) in all patients after therapy. Patients with increased aspirin tolerance showed a significant decrease in urinary leukotriene E4 levels and their improvement in clinical parameters was associated with a reduction of eotaxin-1, C-C motif chemokine ligand 17, IL-5, IL-17A and IL-6. Conclusion: In this study, 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy. Dupilumab improves aspirin hypersensitivity in over 50% of patients with NSAID-exacerbated respiratory disease, and clinical improvement was associated with a reduction in nasal biomarkers http://bit.ly/3goVjB1